{"title":"桑叶中植物化学物质的药代动力学研究、分子对接和分子动力学模拟:结直肠癌潜在治疗药物的多受体方法。","authors":"B Stany, Shatakshi Mishra, K V Bhaskara Rao","doi":"10.1007/s12032-024-02406-5","DOIUrl":null,"url":null,"abstract":"<p><p>This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi receptor approach for potential therapeutic agents in colorectal cancer.\",\"authors\":\"B Stany, Shatakshi Mishra, K V Bhaskara Rao\",\"doi\":\"10.1007/s12032-024-02406-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.</p>\",\"PeriodicalId\":18433,\"journal\":{\"name\":\"Medical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12032-024-02406-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12032-024-02406-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
本研究探讨了从桑白皮中提取的植物化学物质在治疗结直肠癌(CRC)方面的潜力。结直肠癌是一个全球关注的健康问题,死亡率不断上升,因此需要创新的预防和治疗策略。该研究采用硅学分析、分子对接技术(MDT)和分子动力学模拟(MDS),研究了桑白皮提取的植物化学物质与牵涉到 CRC 进展的关键蛋白(AKT1、Src、STAT3、EGFR)之间的相互作用。ADME/T 分析筛选了 78 种植物化学物质的类药物和药代动力学特性。该研究整合了利宾斯基的 "五法则 "和全面的生物活性评估,提供了对桑白皮植物成分作为 CRC 治疗药物潜力的细致理解。值得注意的是,在 78 种植物化学物质中,有 14 种显示出口服生物利用度和良好的生物活性。采用 Autodock 1.5.7 进行能量最小化,然后进行分子对接,观察到 Kuwanon A 与 AKT1 的最高结合能为 - 11.7 kcal/mol。对 Kuwanon A 和 AKT1 在 Pleckstrin 同源(PH)结构域区域(TRP80)进行了分子动力学模拟和轨迹路径分析,结果显示偏差极小。根据计算分析,与标准药物 Capivasertib 相比,植物化学物质 Kuwanon A 是一个突出的候选药物。这表明它有潜力成为一种替代药物,以缓解标准药物的相关局限性。这项研究旨在为未来的实验验证提供见解,并促进 Kuwanon A 作为一种新型、有效的结直肠癌治疗药物的开发。
Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi receptor approach for potential therapeutic agents in colorectal cancer.
This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.
期刊介绍:
Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.